1. Field of the Invention
The invention relates to a process for the production of enantiomerically pure 2,2,4 -trisubstituted 1,3-dioxolanes.
2. Background Art
Enantiomerically pure 2,2,4-trisubstituted 1,3-dioxolanes of the general formula: ##STR2## wherein X is OH or X is NHR.sup.3, as derivatives of glycerin or 3-amino-1,2-propanediol, are extremely valuable chiral building blocks for stereospecific syntheses of natural products and of other optically active compounds, as, for example, pharmaceutical active ingredients. Some examples of these uses are the syntheses of (R)-4-amino-3-hydroxybutyric acid (GABOB) [J. Am. Chem. Soc. 102, 6304 (1980)], L carnitine (European Published Patent Application No. 0,060,595), acyclovir analogs [J. Med. Chem. 28, 926 (1985)] or beta-blockers (German OS No. 2810732).
Although some of these 1,3-dioxolanes, namely, the acetonides of glycerol (R.sup.1 =R.sup.2 =CH.sub.3, X=OH), and some ethers and esters derived from them (X=OCH.sub.2 C.sub.6 H.sub.5, O-tosyl) are already commercially available, the still very high price of these compounds prevents their use to a large extent. The numerous production processes known so far start from expensive feedstock (L-serine, L-arabinose) and/or expensive reagents used [lead(IV) acetate, NaIO.sub.4, bismuth compounds, among others] and, therefore, do not allow production on an industrial scale and at attractive prices for reasons of costs.
A new process for the production of (S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (L-glyceraldehyde acetonide), (European Published Patent Application No. 0,143,973), from which the corresponding hydroxy compound can be obtained by reduction, for example, with sodium tetrahydridoborate, starts from 3,4-O-isopropylidene-L-threonic acid, which is degraded with hypochlorous acid or hypochlorite in an acid medium to the L-glyceraldehyde acetonide. Although 3,4-O-isopropylidene-L-threonic acid starting from L-ascorbic acid is easily available and the hypochlorite solution is a cheap chemical, such process still has some serious drawbacks:
The commercially available hypochlorite solutions vary in content and are not completely stable.
The free hypochlorous acid formed during the conducting of the process is still not very stable and partially decomposes, and, thus, more than the theoretically required amount is consumed.
An excess of hypochlorite still present after the course of the oxidation must be destroyed by the addition of a reduction agent. Thus, other extraneous materials are introduced into the reaction mixture.
The hypochlorite solution is very corrosive and requires a correspondingly resistant material for the apparatus used.
The hypochlorite solution used already contains large amounts of chloride, and further chloride is formed in the reaction. This total chloride amount must finally be disposed of; moreover, working up of the reaction mixture is possibly disturbed by the high salt concentration.
Performing the oxidation in an acid solution in the case of sensitive ketals and especially acetals can lead to hydrolysis of the ketal or acetal function and in these cases can make the process unusable.